title: Retinoic acid receptor alpha: One of plasma biomarkers associated with exacerbation of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Exacerbation of COPD is a major risk factor for bad prognosis of COPD. A few plasma proteins have been discovered to associate with hospital admission due to exacerbation up to date. We tried to find new plasma biomarkers to predict the exacerbation of COPD.
  
  
  METHODS
  We examined the plasma of normal control (n = 8) and COPD stable (n = 8) and exacerbation (n = 8) using 2-Dimentional Electrophoresis. The differentially expressed protein spots were identified by MALDI-TOF. ELISA were performed for quantitative measurement of RARα in plasma from normal control (n = 37) and COPD (n = 35).
  
  
  RESULTS
  17 proteins were differentially expressed in plasma between stable and exacerbation state in the subjects with COPD. Identification using MALDI-TOF showed that retinoic acid receptor alpha, ninein, isoform CRA_a, alpha-1 antitrypsin, fibrinogen gamma, tyrosyl-DNA phosphodiesterase 2, and T cell receptor delta chain were increased in exacerbation of COPD, while fibrin beta, Crystal Structure Of An Autoimmune Complex Between A Human Igm RF* And Igg1 Fc, transferrin, serpin peptidase inhibitor member 6, complement factor B preproprotein, Chain B, Crig Bound To C3c, and WD repeat-containing protein 1 isoform 1 were decreased. Quantitative measurement showed that RARα plasma levels significantly increased in exacerbation state compared to stable state of COPD (n = 14). In the plasma of stable state, the COPD subjects (n = 14) having more than 0.4 time/yr of admission had very high levels of RAR alpha protein and those (n = 11) having less than 0.4 times/yr of admission had the intermediate levels compared to those having no exacerbation (n = 10). ROC analysis of RAR alpha levels to frequency of admission showed an area under the curve of 0.844. A cut-off of 0.154 ng/ml of RAR alpha predicted hospital admission with a sensitivity of 71.4% and a specificity of 92.8%.
  
  
  CONCLUSIONS
  The proteomic analysis of plasma indicates that alteration of several proteins may be associated with admission of COPD. Among them, plasma RAR alpha level may predict hospital admission with a sensitivity of 71.4% and a specificity of 92.8%.
authors.affiliation: 1Division of Allergy and Respiratory Disease, Genome Research Center, Soonchunhyang University, Bucheon Hospital , Gyeonggi-do , Republic of Korea.
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Heo
authors.forename: Jong-Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: An-Soo
authors.initials: AS
authors.lastname: Jang
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Ji-Na
authors.initials: JN
authors.lastname: Kim
authors.forename: Yang Gi
authors.initials: YG
authors.lastname: Kim
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Choi
authors.forename: Joo Ok
authors.initials: JO
authors.lastname: Na
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Jeong
authors.forename: Yong-bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Sung-Ryul
authors.initials: SR
authors.lastname: Kim
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications*; D012372:ROC Curve; D018168:Receptors, Retinoic Acid / Q000097:blood*; D012129:Respiratory Function Tests; D000072482:Retinoic Acid Receptor alpha; D012307:Risk Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha